By developing a large database of BAL fluid linked to specific microbiologic diagnoses, we plan to define protein expression signature response profiles that distinguish specific etiologies of lung infection and inflammation. These signature profiles will be based on mass spectrometry, two-dimensional gel electrophoresis and suspension array technologies. Because of the variability associated with individual host responses to infection due to differences in host immunity, sampling time effects, and external factors such as antibiotic or anti-inflammatory therapies, a large database will be required. The profiles of culture-negative BAL fluid will be of similar interest to assist in defining non-infectious etiologies of lung inflammation. A secondary objective is to perform proteomic analysis on serum collected from patients at the time of bronchoscopy. The goal is to link serum proteomic profiles to BAL proteomic profiles to determine whether a less invasive technique can predict infiltrate etiology with comparable sensitivity and specificity to BAL profiles. To complement the patient studies we have investigated protein biomarkers in blood and lavage from animal models of pneumonia. We have studied a rabbit model of invasive pulmonary aspergillosis (Proteomics 2010;10: 4270-4280) and a canine model of staphylococcal pneumonia (Am J Physiol Heart Circ Physiol 2007;293;H2487-500). Exploring these model systems will facilitate our identification of candidate biomarkers across species. A total of 587 cases have been enrolled in this study to date. Approximately one half of the participants have a specific microbiologic diagnosis as a cause of their pulmonary infiltrates. Enrollment thus far in the cases of interest includes: Aspergillus species 58, P. jiroveci 62, Cytomegalovirus 61, Mycobacterial species 41, and Bacteria (gram negative or gram positive) 117. Approximately 50-60% of these infections occur with more than one microbial pathogen (i.e. Aspergillus species and cytomegalovirus). Infections with only a single pulmonary pathogen are somewhat less common than co-infection states. New samples of the bronchoalveolar lavage and blood are currently being analyzed.